NYMC Faculty Publications
DOI
10.1074/jbc.RA118.002925
Journal Title
The Journal of Biological Chemistry
First Page
8255
Last Page
8263
Document Type
Article
Publication Date
5-1-2018
Department
Biochemistry and Molecular Biology
Abstract
Cellular thiols such as cysteine spontaneously and readily react with the respiratory intermediate fumarate, resulting in the formation of stable S-(2-succino)-adducts. Fumarate-mediated succination of thiols increases in certain tumors and in response to glucotoxicity associated with diabetes. Therefore, S-(2-succino)-adducts such as S-(2-succino)cysteine (2SC) are considered oncometabolites and biomarkers for human disease. No disposal routes for S-(2-succino)-compounds have been reported prior to this study. Here, we show that Bacillus subtilis metabolizes 2SC to cysteine using a pathway encoded by the yxe operon. The first step is N-acetylation of 2SC followed by an oxygenation that we propose results in the release of oxaloacetate and N-acetylcysteine, which is deacetylated to give cysteine. Knockouts of the genes predicted to mediate each step in the pathway lose the ability to grow on 2SC as the sulfur source and accumulate the expected upstream metabolite(s). We further show that N-acetylation of 2SC relieves toxicity. This is the first demonstration of a metabolic disposal route for any S-(2-succino)-compound, paving the way toward the identification of corresponding pathways in other species.
Recommended Citation
Niehaus, T., Folz, J., McCarty, D., Cooper, A., Moraga Amador, D., Fiehn, O., & Hanson, A. (2018). Identification of a Metabolic Disposal Route for the Oncometabolite S-(2-succino)cysteine in Bacillus subtilis. The Journal of Biological Chemistry, 293 (21), 8255-8263. https://doi.org/10.1074/jbc.RA118.002925
Publisher's Statement
Originally published in The Journal of Biological Chemistry, 293(21), 8255-8263. The original material can be found here.